Effect of Helicobacter pylori eradication on gastric carcinogenesis.

Romero-Gallo J, Harris EJ, Krishna U, Washington MK, Perez-Perez GI, Peek RM
Lab Invest. 2008 88 (3): 328-36

PMID: 18180700 · PMCID: PMC2833422 · DOI:10.1038/labinvest.3700719

Chronic gastritis induced by Helicobacter pylori is the strongest known risk factor for gastric adenocarcinoma, yet the effects of bacterial eradication on carcinogenesis remain unclear. Animal models provide important insights into factors that are involved in gastric carcinogenesis, and we previously utilized such a model to demonstrate that an in vivo-adapted H. pylori strain, 7.13, rapidly and reproducibly induces inflammation-mediated gastric carcinoma. In the current study, we used this bacterial strain as a prototype to define the role of targeted antimicrobial therapy in gastric carcinogenesis. Mongolian gerbils were infected with H. pylori for 4 or 8 weeks, treated with antimicrobial agents or vehicle, and then euthanized at 8 weeks after the completion of therapy. All infected gerbils developed gastritis; however, inflammation was significantly attenuated in animals receiving antimicrobial therapy. Gastric dysplasia or cancer developed in >60% of the gerbils that remained persistently colonized with H. pylori, but in none of the animals treated with antibiotics following 4 weeks of infection. Infection with H. pylori for 8 weeks prior to therapy resulted in an attenuation, but not complete prevention, of pre-malignant and malignant lesions. Similarly, antibiotic therapy initiated at 4, but not 8, weeks after H. pylori challenge significantly reduced expression of the Th1 pro-inflammatory cytokine interferon-gamma within colonized gastric mucosa. These results indicate that treatment of H. pylori in this model decreases the incidence and severity of lesions with carcinogenic potential. The effectiveness of eradication is dependent upon the timing of intervention, providing insights into mechanisms that may regulate the development of malignancies arising within the context of inflammatory states.

MeSH Terms (20)

2-Pyridinylmethylsulfinylbenzimidazoles Adenocarcinoma Amoxicillin Animals Animals, Outbred Strains Anti-Bacterial Agents Clarithromycin Disease Models, Animal Drug Administration Schedule Drug Therapy, Combination Gastritis Gerbillinae Helicobacter Infections Helicobacter pylori Interferon-gamma Lansoprazole Male Specific Pathogen-Free Organisms Stomach Neoplasms Time Factors

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